Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL

NCT ID: NCT02557516

Last Updated: 2019-12-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-09
• Study Completion Date: 2019-09-25

Brief Summary

Combination study of monalizumab (IPH2201) with Ibrutinib in relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia (CLL) patients in 2 parts :

• phase 1 : a 3+3 design to assess the Maximum Tolerated Dose (MTD)
• phase 2: to evaluate the anti-leukemic activity of the combination

Detailed Description

This trial was designated to test the hypothesis that the combination of ibrutinib and IPH2201 will result in a substantial complete response (CR) rate, especially CR without minimal residual disease (MRD), as this has been shown to be associated with long-term clinical benefit.

Up to 45 patients were planned to be enrolled. During the phase 1 part a 3+3 dose escalation design was employed. Four doses were planned to be assessed if the Maximum Tolerated Dose (MTD) was not previously reached: 1, 2, 4 and 10 mg/kg.

During phase 2 part, patients received monalizumab in combination with ibrutinib; monalizumab was given at the dose recommended upon completion of the phase I portion.

The primary objective of the phase 1 was to assess the safety of monalizumab given intravenously as a single agent and in combination with ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.

The primary objective of the phase 2 was to evaluate the anti-leukemic activity of the combination of monalizumab and ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Level 1 - 1 mg/kg

In phase 1, Monalizumab given at the first dose level of 1 mg/kg.

Group Type: EXPERIMENTAL

monalizumab

Intervention Type: DRUG

During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks.

During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.

Phase 1 Level 2 - 2 mg/kg

In phase 1, Monalizumab given at the second dose level of 2 mg/kg.

Group Type: EXPERIMENTAL

monalizumab

Intervention Type: DRUG

During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks.

During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.

Phase 1 Level 3 - 4 mg/kg

In phase 1, Monalizumab given at the third dose level of 4 mg/kg.

Group Type: EXPERIMENTAL

monalizumab

Intervention Type: DRUG

During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks.

During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.

Phase 2 RP2D - 2 mg/kg

In phase 2, Monalizumab given at the Recommended Phase 2 Dose (RP2D) of 2 mg/kg, selected by a safety committee.

Group Type: EXPERIMENTAL

monalizumab

Intervention Type: DRUG

During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks.

During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.

Interventions

monalizumab

During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks.

During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.

Intervention Type: DRUG

Other Intervention Names

Anti-NKG2A; IPH2201

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
• Relapsed, refractory or previously untreated CLL
• CLL requiring treatment; patients must be eligible for ibrutinib therapy
• Age > = 18 years
• Eastern Cooperative Oncology Group performance status of 0-2
• Life expectancy > = 3 months
• Adequate liver and renal function
• Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study participation
• Ability to understand a written informed and consent document
• Signed informed consent prior to any protocol-specific procedures

Exclusion Criteria

• Patients who have previously received ibrutinib or another inhibitor of Bruton's tyrosine kinase (BTK)
• History of allergic reactions attributed to compounds or similar chemical or biological composition to ibrutinib
• Central nervous system involvement of the CLL
• Abnormal hematological function which is not due to bone marrow failure related to the CLL
• Patients requiring a treatment by oral vitamin K antagonists
• Serious uncontrolled medical disorder
• Medical condition or organ system dysfunction which, in the investigator opinion, could interfere with absorption or metabolism of ibrutinib
• Moderate or severe hepatic impairment
• Active auto-immune disease
• Abnormal cardiac status
• Pregnant women are excluded from study
• Current active infectious disease
• History of another malignancy within 3 years
• History of allogeneic stem cell or solid organ transplantation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innate Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kerry A Rogers, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Countries

United States

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

IPH2201-202

Identifier Type: -

Identifier Source: org_study_id